title: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers.
abstract: Immunosuppressive therapy is frequently associated with hypercholesterolemia, calling for lipid-lowering treatment without adverse drug interactions. One option is treatment with the cholesterol absorption inhibitor ezetimibe. We have shown in vitro that ezetimibe and tacrolimus may interact in competition for intestinal UGT1A1 and ABCB1 at concentrations reached in gut lumen after oral administration. However, this clinical study in healthy volunteers showed that the expected pharmacokinetic interaction between ezetimibe and tacrolimus is not of clinical relevance.
authors.affiliation: Department of Clinical Pharmacology, University of Greifswald, Greifswald, Germany. stefan.oswald@uni-greifswald.de
authors.forename: S
authors.initials: S
authors.lastname: Oswald
authors.forename: A
authors.initials: A
authors.lastname: Nassif
authors.forename: C
authors.initials: C
authors.lastname: Modess
authors.forename: M
authors.initials: M
authors.lastname: Keiser
authors.forename: A
authors.initials: A
authors.lastname: Ulrich
authors.forename: D
authors.initials: D
authors.lastname: Runge
authors.forename: U
authors.initials: U
authors.lastname: Hanke
authors.forename: D
authors.initials: D
authors.lastname: Lütjohann
authors.forename: A
authors.initials: A
authors.lastname: Engel
authors.forename: W
authors.initials: W
authors.lastname: Weitschies
authors.forename: W
authors.initials: W
authors.lastname: Siegmund
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001384:Azetidines / Q000493:pharmacokinetics* / Q000494:pharmacology; D002460:Cell Line; D018592:Cross-Over Studies; D004285:Dogs; D004347:Drug Interactions; D000069438:Ezetimibe; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000494:pharmacology; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000924:Anticholesteremic Agents; D001384:Azetidines; D000069438:Ezetimibe; D014453:Glucuronosyltransferase; D007166:Immunosuppressive Agents; D016559:Tacrolimus; D000099148:UGT1A1 Enzyme; C513055:ABCB1 protein, human